1. Field of the Invention
This invention relates to a method of treating a patient with an orally administrable time release drug product. In particular, it relates to a drug product that will be time released in a patient. The drug product may be used therapeutically, prophylactically and diagnostically for diseases wherein a general continuous level of drug concentration in the blood stream is desired.
2. Description of the Prior Art
It is known to provide orally administrable drugs in liquid suspensions, tablets and capsules. It is also known to provide a plurality of time-release drugs in treating, for example, the symptoms of a cold. One of the problems with the orally administrable drug form is the fact that the drug has a short half-life thereby requiring frequent administration of the drug in an effort to achieve the desired blood concentration. Another difficulty with frequent dosing is that the cycles of concentration cover a wide range which not only fails to produce a steady state of ingredients of drug but can give undesired side effects.
For the orally administrable non-steroidal anti-inflammatory drug, diclofenac sodium, commonly employed in the long term treatment of rheumatic disorders, many problems are known. This drug is typically completely absorbed following oral administration and its elimination half-life is 1 to 2 hours. Repeated oral administration of diclofenac sodium in long term therapy cases frequently causes gastrointestinal disturbances and may cause kidney failure. Due to the biopharmaceutical and pharmacological properties of the drug, a controlled time-release form is desirable. Gupta studied the controlled release of microspheres of diclofenac sodium prepared by spherical crystallization technique. Gupta, V. K., Jayaswal, S. B. Srivastava, A. K. and Kumar, M. V., "Controlled release microspheres of diclofenac sodium prepared by spherical crystallization technique." Pharmazie, 49 (1994) 692-693. Guterres investigated a formulation and stability study of Poly(DL-lactide) nanocapsules containing diclofenac. Guterres, S. S., Fessi, H., Barratt, G., Devissaguet, J. P. and Puisieux, F. "Poly(DL-lactide) nanocapsules containing diclofenac: I. Formation and stability study." Int. J. Pharm., 113 (1995) 57-63. Hirotani studied the preparation of controlled-release granules of sodium diclofenac. Hirotani, Y., Arakawa, Y., Maeda, Y. Yamaji, A., Kamada, A and Nishihata, T., "Preparation of controlled-release granules of sodium diclofenac." Chem. Pharm. Bull., 35 (1987) 3049-3053. Ichikawa has investigated the coating of pharmaceutical powders by a fluidized bed process. Ichikawa, H., Tokomutsu, H., Jono, K. Fukuda, T., Osako, Y and Fukomori, Y., "Coating of pharmaceutical powders by fluidized bed process. VI. microencapsulation using blend and composite lattices of copoly(ethyl acrylate-methyl methacrylate-2-hydroxyethyl methacrylate). Chem Pharm. Bull., 42 (1994) 1308-1314. Sagara has studied the bioavailability of commercial sustained-release preparations of diclofenac sodium in gastro-intestinal physiology related drugs. Sagara, K., Nagamatsu, Y., Yamada, I., Kawata, M., Mizuta, H. and Ogawa, K., "Bioavailability study of commercial sustained-release preparations of diclofenac sodium in gastro-intestinal physiology regulated-dogs." Chem. Pharm. Bull., 40 (1992) 3303-3306. Sagara's technology uses only one layer which is a methacrylic acid copolymer.
In spite of the prior art disclosures, there remains a very real and substantial need for a prolonged time-release drug and method of treating a patient with the drug that has prolonged time-release properties so that the desired steady state in the bloodstream will be achieved.